Composition containing oxidation-sensitive hydrophilic active principle and maleic anhydride copolymer, and use thereof

ABSTRACT

The invention relates to the use of a composition, especially for preventing and/or treating cutaneous signs of intrinsic ageing, the composition containing at least one oxidation-sensitive hydrophilic active principle selected from the group consisting of ascorbic acid and its compounds and at least one maleic anhydride copolymer.

REFERENCE TO PRIOR APPLICATIONS

[0001] This application claims priority to U.S. Provisional application No. 60/394,255, filed Jul. 9, 2002, and to French patent application 0207638, filed Jun. 20, 2002, both of which are incorporated herein by reference.

SUMMARY OF THE INVENTION

[0002] The present invention relates to the use, preferably the cosmetic and/or dermatological use, of a composition comprising at least one oxidation-sensitive hydrophilic active principle and at least one maleic anhydride copolymer in a physiologically acceptable medium comprising an aqueous phase. Preferably the use is for preventing and/or treating cutaneous signs of intrinsic ageing. The compositions described also make up a part of the invention.

DISCUSSION OF THE BACKGROUND

[0003] It is known to introduce, into cosmetic compositions, various active principles intended to contribute specific treatments to the skin and/or hair. However, some of these active principles exhibit the disadvantage of being unstable in an aqueous medium and of easily decomposing on contact with water, in particular because of oxidation phenomena. They thus rapidly lose their activity over time and this instability conflicts with the desired effectiveness.

[0004] Attempts have thus been made for a long time to formulate ascorbic acid or vitamin C because of its numerous beneficial properties. In particular, ascorbic acid stimulates the synthesis of the connective tissue and in particular of collagen, strengthens the defences of the cutaneous tissue against external attacks, such as ultraviolet radiation and pollution, compensates for vitamin E deficiency of the skin, depigments the skin and has a role in combating free radicals. These last two properties make it an excellent candidate as cosmetic or dermatological active principle for combating ageing of the skin or for preventing ageing of the skin. Unfortunately, because of its chemical structure (of α-ketolactone), ascorbic acid is highly sensitive to certain environmental parameters and in particular to oxidation phenomena. There thus ensues rapid decomposition of formulated ascorbic acid in the presence of these parameters and in particular in the presence of oxygen, light or metal ions, as a function of the temperature or under certain pH conditions (Pharm. Acta. Helv., 1969, 44, 611-667; STP Pharma, 1985, 4, 281-286).

[0005] Several solutions have thus been envisaged in the prior art for reducing and/or slowing down the decomposition of ascorbic acid.

[0006] Provision has thus been made to use ascorbic acid in the form of a compound thereof (sometimes referred to as a derivative or chemical derivative thereof) (magnesium ascorbyl phosphate or esters of fatty acids and ascorbic acid), but the bioavailability of these compounds is very low (J. Am. Acad. Dermatol., 1996, 34, 29-33).

[0007] The instability of ascorbic acid with respect to oxygen can be improved by using specific packagings, such as twin compartments under an inert atmosphere, as disclosed in Patent U.S. Pat. No. 5,935,584, or alternatively by the use of two-phase emulsions, one phase of which is composed of a dry powder comprising ascorbic acid and the second phase of which is a liquid phase. The mixing of the two phases has to be carried out at the time of use (WO 98/43598). These solutions have disadvantages with regard to the cost and the complexity of the manufacturing operations and significant restrictions with regard to use.

[0008] Another solution provided in the prior art consists in using a high concentration of glycols or polyols in order to reduce the solubility of oxygen in the formulation, thus protecting the ascorbic acid (WO 96/24325, EP 0 755 674, U.S. Pat. No. 5,981,578). The polyols can optionally be incorporated in liposomes, as disclosed in Patent U.S. Pat. No. 6,020,367. However, these solutions exhibit the disadvantage of resulting in sticky formulations, the cosmetic quality of which is difficult to improve. Furthermore, the presence of a high concentration of these compounds can lead to phenomena of irritation.

[0009] Ascorbic acid can also be formulated in anhydrous media, such as silicones (U.S. Pat. No. 6,194,452), which are capable of creating an anhydrous barrier around ascorbic acid. A major disadvantage of such solutions results from the lack of freshness on application.

DEETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The need thus remains for a composition employable in particular in the cosmetics field, in which a hydrophilic active principle which is unstable in an oxidizing medium is stabilized, which is comfortable on application, which does not lead to any skin irritation after application and which is compatible with the constraints of an industrial implementation of its manufacturing process.

[0011] The effect of ascorbic acid on the biosynthesis of collagen, a protein macromolecule predominantly present in the dermis, has been known for several years (Arch. Biochem. Biophys., 152, 1972, p. 318-328). It acts at two levels. First of all, as cofactor of hydroxylases, enzymes involved in the hydroxylation of proline and of lysine, ascorbic acid promotes this essential stage in the assembling of procollagen molecules (Biochemistry, 78(5), 1981, p. 2279-2282; The Yale Journal of Biology and Medecine, 58, 1985, p. 553-559). Furthermore, it stimulates the biosynthesis of collagen by increasing the amount of mRNA coding for procollagens of type I and III (The Journal of Investive Dermatology, 90(4), 1988, p. 420-424).

[0012] Magnesium ascorbyl phosphate also stimulates the synthesis of collagen (Skin Pharmacol., 6, 1993, p. 65-71).

[0013] At the same time as these properties, the ascorbic acid used to treat cutaneous fibroblasts has made it possible to demonstrate an increase in proteoglycans (Journal of Biochemical Engineering, 1991, 113).

[0014] More recently, the Applicant Company has shown that magnesium ascorbyl phosphate, added to a medium for the culturing of reconstructed skin, led to a significant increase in the number of fibroblasts in the lattice, in combination with significant stimulation of the synthesis of proteins of the extracellular matrix (FR-02/01510). This was observed in particular at the dermoepidermal junction, where stimulation of the synthesis of the major components, which are collagens IV and VII, and laminin, is measured. This phenomenon has the consequence of reinforcing the relief of this junction, promoting exchanges between dermis and epidermis, and the cohesion of these two tissues, and thus makes it possible to combat the harmful effects of ageing on these factors.

[0015] By enhancing the overall content of collagen, the proliferative capability and the synthetic activity of fibroblasts and the amount of procollagen I and III, but also by reinforcing the cohesion and the effectiveness of the dermoepidermal junction, ascorbic acid and its compounds are therefore particularly useful in preventing and/or treating cutaneous signs of intrinsic ageing.

[0016] One object of the present invention is to provide a composition comprising an oxidation-sensitive active principle selected from the group consisting of ascorbic acid and its compounds, which exhibits good cosmetic properties, both with regard to touch and with regard to tolerance, the preservation of which over time does not require specific precautions, and which retains the activity of the active principle in the prevention and/or the treatment of cutaneous signs of intrinsic ageing.

[0017] The inventor has discovered, fortuitously, that the use of maleic anhydride copolymers in compositions in which the aqueous phase includes an oxidation-sensitive active principle, such as ascorbic acid, makes it possible to achieve the abovementioned aim.

[0018] To the knowledge of the inventor, such polymers comprising maleic anhydride units have never been used in combination with hydrophilic active principles sensitive to decomposition by oxidation for the purpose of improving their stability. This is true in particular in the case of ascorbic acid.

[0019] A subject-matter of the present invention is therefore the cosmetic and/or dermatological use of a composition for preventing and/or treating cutaneous signs of intrinsic ageing, the composition comprising at least one oxidation-sensitive hydrophilic active principle selected from the group consisting of ascorbic acid and its compounds and at least one maleic anhydride copolymer in a physiologically acceptable medium comprising an aqueous phase. The copolymer is present in an amount sufficient to stabilize the oxidation-sensitive hydrophilic active principle. Preferably, the oxidation-sensitive active principle and the copolymer are both in the aqueous phase.

[0020] Another subject-matter of the present invention is the use of a combination composed of at least one oxidation-sensitive hydrophilic active principle selected from the group consisting of ascorbic acid and its compounds and of at least one maleic anhydride copolymer in a cosmetic composition comprising an aqueous phase as agent for preventing and/or treating cutaneous signs of intrinsic ageing.

[0021] Another aspect of the invention relates to the use of at least one oxidation-sensitive hydrophilic active principle selected from the group consisting of ascorbic acid and its compounds and of at least one maleic anhydride copolymer in the preparation of a dermatological composition comprising an aqueous phase intended for preventing and/or treating cutaneous signs of intrinsic ageing.

[0022] According to the invention, the term “hydrophilic active principle” is understood to mean a compound having a solubility in water of at least 0.25% at ambient temperature (25° C.).

[0023] According to the invention, the term “oxidation-sensitive hydrophilic active principle” is understood to mean any active principle of natural or synthetic origin capable of undergoing decomposition by an oxidation mechanism. This oxidation phenomenon can have several causes, in particular the presence of oxygen, of light or of metal ions, a high temperature or certain pH conditions.

[0024] Mention may be made, among ascorbic acid compounds, by way of example and without implied limitation, of: the salts or esters, in particular the 5,6-di-O-dimethylsilylascorbate (sold by Exsymol under the reference PRO-AA), the potassium salt of dl-α-tocopheryl dl-ascorbyl phosphate (sold by Senju Pharmaceutical under the reference SEPIVITAL EPC), magnesium ascorbyl phosphate, sodium ascorbyl phosphate (sold by Roche under the reference Stay-C 50) and ascorbyl glucoside (sold by Hayashibara).

[0025] In a particularly advantageous aspect, the oxidation-sensitive hydrophilic active principle is ascorbic acid.

[0026] According to the invention, the term “maleic anhydride copolymer” is understood to mean any polymer obtained by copolymerization of one or more maleic anhydride comonomers and of one or more comonomers selected from the group consisting of vinyl acetate, vinyl alcohol, vinylpyrrolidone, olefins comprising from 2 to 20 carbon atoms, such as octadecene, ethylene, isobutylene, diisobutylene or isooctylene, and styrene, the maleic anhydride comonomers optionally being partially or completely hydrolysed. Use will preferably be made of hydrophilic polymers, that is to say polymers having a solubility in water of greater than or equal to 2 g/l.

[0027] Copolymers which are more particularly suitable for the implementation of the invention are copolymers obtained by copolymerization of one or more maleic anhydride units and in which the maleic anhydride units are in the hydrolysed form and preferably in the form of alkaline salts, for example in the form of ammonium, sodium, potassium or lithium salts.

[0028] In an advantageous aspect of the invention, the copolymer has a molar fraction of maleic anhydride units of between 0.1 and 1, more preferably between 0.4 and 0.9.

[0029] According to an advantageous aspect of the invention, the molar ratio of the maleic anhydride unit equivalent to the oxidation-sensitive hydrophilic active principle varies between 0.005 and 10 and preferably between 0.01 and 1.

[0030] The weight-average molar mass (molecular weight) of the maleic anhydride copolymers will advantageously be between 1 000 and 500 000 and preferably between 1 000 and 50 000.

[0031] Use will preferably be made of a copolymer of styrene and of maleic anhydride in a 50/50 ratio.

[0032] Use may be made, for example, of the styrene/maleic anhydride (50/50) copolymer in the form of a 30% ammonium salt in water sold under the reference SMA1000H® by Atofina or the styrene/maleic anhydride (50/50) copolymer in the form of a 40% sodium salt in water sold under the reference SMA1000HNa® by Atofina.

[0033] The copolymer is present in the composition according to the invention in an amount sufficient to produce the desired effect, that is to say in an amount sufficient to stabilize the oxidation-sensitive hydrophilic active principle. Preferably, the copolymer is present at a concentration of between 0.1 and 40% by weight with respect to the total weight of the aqueous phase and more particularly at a concentration of between 0.1 and 10% by weight with respect to the total weight of the aqueous phase.

[0034] The compositions used according to the invention are intended for topical application to the skin and/or its superficial body growths and therefore comprise a physiologically acceptable medium, that is to say a medium compatible with cutaneous tissues, such as the skin, scalp, eyelashes, eyebrows, hair, nails and mucous membranes. This physiologically acceptable medium may more particularly be composed of water and optionally of a physiologically acceptable organic solvent chosen, for example, from lower alcohols comprising from 1 to 8 carbon atoms and in particular from 1 to 6 carbon atoms, such as ethanol, isopropanol, propanol or butanol; polyethylene glycols having from 6 to 80 ethylene oxide units; or polyols, such as propylene glycol, isoprene glycol, butylene glycol, glycerol or sorbitol.

[0035] When the physiologically acceptable medium is an aqueous medium, it generally has a pH which is compatible with the skin, preferably ranging from 3 to 9 and better still from 3.5 to 7.5.

[0036] The compositions according to the invention can be provided in any pharmaceutical dosage form used conventionally for topical application and in particular in the form of aqueous or aqueous/alcoholic solutions, of oil-in-water (O/W) or water-in-oil (W/O) or multiple (triple: W/O/W or O/W/O) emulsions, of aqueous gels or of dispersions of a fatty phase in an aqueous phase using spherules, it being possible for these spherules to be polymeric nanoparticles, such as nanospheres and nanocapsules, or lipid vesicles of ionic and/or nonionic type (liposomes, niosomes or oleosomes). These compositions are prepared according to the usual methods.

[0037] In addition, the compositions used according to the invention can be more or less fluid and can have the appearance of a white or coloured cream, of an ointment, of a milk, of a lotion, of a serum, of a paste or of a foam. They can optionally be applied to the skin in the form of an aerosol. They can also be provided in a solid form, for example in the form of a stick.

[0038] When the composition used according to the invention comprises an oily phase, the latter preferably comprises at least one oil. It can additionally comprise other fatty substances.

[0039] Mention may be made, as oils which can be used in the composition of the invention, of, for example:

[0040] hydrocarbonaceous oils of animal origin, such as perhydrosqualene;

[0041] hydrocarbonaceous oils of vegetable origin, such as liquid triglycerides of fatty acids comprising from 4 to 10 carbon atoms, such as triglycerides of heptanoic acid or octanoic acid, or alternatively, for example, sunflower, maize, soybean, gourd, grape seed, sesame, hazelnut, apricot, macadamia, arara, castor or avocado oils, triglycerides of caprylic/capric acids, such as those sold by Stéarineries Dubois or those sold under the names Miglyol 810, 812 and 818 by Dynamit Nobel, jojoba oil, or karite butter oil;

[0042] synthetic esters and ethers, in particular of fatty acids, such as the oils of formulae R¹COOR² and R¹OR² in which R¹ represents the residue of a fatty acid comprising from 8 to 29 carbon atoms and R² represents a branched or unbranched hydrocarbonaceous chain comprising from 3 to 30 carbon atoms, such as, for example, purcellin oil, isononyl isononanoate, isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl stearate, 2-octyldodecyl erucate or isostearyl isostearate; hydroxylated esters, such as isostearyl lactate, octyl hydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, triisocetyl citrate or heptanoates, octanoates or decanoates of fatty alcohols; polyol esters, such as propylene glycol dioctanoate, neopentyl glycol diheptanoate and diethylene glycol diisononanoate; and pentaerythritol esters, such as pentaerythrityl tetraisostearate;

[0043] linear or branched hydrocarbons of mineral or synthetic origin, such as volatile or nonvolatile liquid paraffins and their compounds, liquid petrolatum, polydecenes or hydrogenated polyisobutene, such as parleam oil;

[0044] fatty alcohols having from 8 to 26 carbon atoms, such as cetyl alcohol, stearyl alcohol and their mixture (cetearyl alcohol), octyldodecanol, 2-butyloctanol, 2-hexyldecanol, 2-undecylpentadecanol, oleyl alcohol or linoleyl alcohol;

[0045] partially hydrocarbon-comprising and/or silicone-comprising fluorinated oils, such as those disclosed in the document JP-A-2-295912;

[0046] silicone oils, such as volatile or nonvolatile polymethylsiloxanes (PDMS) comprising a linear or cyclic silicone chain which are liquid or pasty at ambient temperature, in particular cyclopolydimethylsiloxanes (cyclomethicones), such as cyclohexasiloxane; polydimethylsiloxanes comprising pendent alkyl, alkoxy or phenyl groups or alkyl, alkoxy or phenyl groups at the end of the silicone chain, which groups have from 2 to 24 carbon atoms; or phenylated silicones, such as phenyl trimethicones, phenyl dimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl dimethicones, diphenylmethyldiphenyltrisiloxanes, (2-phenylethyl)trimethylsiloxysilicates and polymethylphenylsiloxanes;

[0047] their mixtures.

[0048] The term “hydrocarbonaceous oil” is understood to mean, in the list of the oils mentioned above, any oil predominantly comprising carbon and hydrogen atoms and optionally ester, ether, fluorinated, carboxylic acid and/or alcohol groups.

[0049] The other fatty substances which can be present in the oily phase are, for example, fatty acids comprising from 8 to 30 carbon atoms, such as stearic acid, lauric acid, palmitic acid and oleic acid; waxes, such as lanolin, beeswax, carnauba or candelilla wax, paraffin or lignite waxes or microcrystalline waxes, ceresin or ozokerite, or synthetic waxes, such as polyethylene waxes or Fischer-Tropsch waxes; silicone resins, such as trifluoromethyl C₁₋₄ alkyl dimethicone and trifluoropropyl dimethicone; and silicone elastomers, such as the products sold under the names “KSG” by Shin-Etsu, under the names “Trefil”, “BY29” or “EPSX” by Dow Corning or under the names “Gransil” by Grant Industries.

[0050] These fatty substances can be chosen in a way varied by a person skilled in the art in order to prepare a composition having the desired properties, for example of consistency or of texture.

[0051] According to a specific embodiment of the invention, the composition according to the invention is a water-in-oil (W/O) or oil-in-water (O/W) emulsion. The proportion of the oily phase in the emulsion can range from 5 to 80% by weight and preferably from 5 to 50% by weight with respect to the total weight of the composition.

[0052] The emulsions generally comprise at least one emulsifier selected from the group consisting of amphoteric, anionic, cationic or nonionic emulsifiers, used alone or as a mixture, and optionally a coemulsifier. The emulsifiers are appropriately chosen according to the emulsion to be obtained (W/O or O/W). The emulsifier and the coemulsifier are generally present in the composition in a proportion ranging from 0.3 to 30% by weight and preferably from 0.5 to 20% by weight with respect to the total weight of the composition.

[0053] Mention may be made, for the W/O emulsions, for example, as emulsifiers, of dimethicone copolyols, such as the mixture of cyclomethicone and of dimethicone copolyol sold under the name “DC 5225 C” by Dow Corning, and alkyl dimethicone copolyols, such as the laurylmethicone copolyol sold under the name “Dow Corning 5200 Formulation Aid” by Dow Corning and the cetyl dimethicone copolyol sold under the name Abil EM 90^(R) by Goldschmidt. Use may also be made, as surfactant of W/O emulsions, of a crosslinked solid organopolysiloxane elastomer comprising at least one oxyalkylenated group, such as those obtained according to the procedure of Examples 3, 4 and 8 of the document U.S. Pat. No. 5,412,004 and the examples of the document U.S. Pat. No. 5,811,487, in particular the product of Example 3 (synthetic example) of Patent U.S. Pat. No. 5,412,004, and such as that sold under the reference KSG 21 by Shin Etsu.

[0054] Mention may be made, for the O/W emulsions, for example, as emulsifiers, of nonionic emulsifiers, such as esters of fatty acids and of glycerol which are oxyalkylenated (more particularly polyoxyethylenated); esters of fatty acids and of sorbitan which are oxyalkylenated; esters of fatty acids which are oxyalkylenated (oxyethylenated and/or oxypropylenated); ethers of fatty alcohols which are oxyethylenated (oxyethylenated and/or oxypropylenated); sugar esters, such as sucrose stearate; and their mixtures, such as the mixture of glyceryl stearate and of PEG-40 stearate.

[0055] In a known way, the cosmetic or dermatological composition of the invention can also comprise adjuvants conventional in the cosmetics or dermatological field, such as hydrophilic or lipophilic gelling agents, preservatives, solvents, fragrances, fillers, UV screening agents, bactericides, odour absorbers, colouring materials, plant extracts or salts. The amounts of these various adjuvants are those conventionally used in the field under consideration, for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase and/or into the lipid spherules.

[0056] Mention may be made, as fillers which can be used in the composition of the invention, for example, of pigments, silica powder; talc; particles of polyamide and in particular those sold under the name Orgasol by Atochem; polyethylene powders; microspheres based on acrylic copolymers, such as those made of ethylene glycol dimethacrylate/lauryl methacrylate copolymer which are sold by Dow Corning under the name Polytrap; expanded powders, such as hollow microspheres and in particular the microspheres sold under the name Expancel by Kemanord Plast or under the name Micropearl F 80 ED by Matsumoto; silicone resin microbeads, such as those sold under the name Tospearl by Toshiba Silicone; and their mixtures. These fillers can be present in amounts ranging from 0 to 20% by weight and preferably from 1 to 10% by weight with respect to the total weight of the composition.

[0057] According to a preferred embodiment, the compositions in accordance with the invention can additionally comprise at least one organic photoprotective agent and/or at least one inorganic photoprotective agent which is active in the UV-A and/or UV-B regions (absorbers), which are soluble in water or in fats or else are insoluble in the cosmetic solvents commonly used, and which are selected from the group consisting of the following agents, denoted below under their INCI name:

[0058] p-aminobenzoic acid (PABA) compounds, in particular PABA, ethyl PABA, ethyl dihydroxypropyl PABA, ethylhexyl dimethyl PABA (sold in particular under the name “Escalol 507” by ISP), glyceryl PABA or PEG-25 PABA (sold under the name “Uvinul P25” by BASF),

[0059] salicylic compounds, in particular homosalate (sold under the name “Eusolex HMS” by Rona/EM Industries), ethylhexyl salicylate (sold under the name “Neo Heliopan OS” by Haarmann and Reimer), dipropylene glycol salicylate (sold under the name “Dipsal” by Scher), or TEA salicylate (sold under the name “Neo Heliopan TS” by Haarmann and Reimer),

[0060] dibenzoylmethane compounds, in particular butyl methoxydibenzoylmethane (sold in particular under the trade name “Parsol 1789” by Hoffmann-LaRoche), or isopropyl dibenzoylmethane,

[0061] cinnamic compounds, in particular ethylhexyl methoxycinnamate (sold in particular under the trade name “Parsol MCX” by Hoffmann-LaRoche), isopropyl methoxycinnamate, isoamyl methoxycinnamate (sold under the trade name “Neo Heliopan E 1000” by Haarmann and Reimer), cinoxate, DEA methoxycinnamate, diisopropyl methyl cinnamate, or glyceryl ethylhexanoate dimethoxycinnamate,

[0062] β,β-diphenylacrylate compounds, in particular octocrylene (sold in particular under the trade name “Uvinul N539” by BASF) or etocrylene (sold in particular under the trade name “Uvinul N35” by BASF),

[0063] benzophenone, in particular benzophenone-1 (sold under the trade name “Uvinul 400” by BASF), benzophenone-2 (sold under the trade name “Uvinul D50” by BASF), benzophenone-3 or oxybenzone (sold under the trade name “Uvinul M40” by BASF), benzophenone-6 (sold under the trade name “Helisorb 11” by Norquay), benzophenone-8 (sold under the trade name “Spectra-Sorb UV-24” by American Cyanamid), benzophenone-12, or n-hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate,

[0064] benzylidene camphor compounds, in particular 3-benzylidene camphor (manufactured under the name “Mexoryl SD” by Chimex), 4-methylbenzylidene camphor (sold under the name “Eusolex 6300” by Merck), or polyacrylamidomethyl benzylidene camphor (manufactured under the name “Mesoryl SW” by Chimex),

[0065] triazine compounds, in particular anisotriazine (sold under the trade name “Tinosorb S” by Ciba Specialty Chemicals), ethylhexyl triazone (sold in particular under the trade name “Uvinul T150” by BASF), diethylhexyl butamido triazone (sold under the trade name “Uvasorb HEB” by Sigma 3V) or 2,4,6-tris(diisobutyl 4′-amino-benzalmalonate)-s-triazine,

[0066] benzotriazole compounds, in particular drometrizole trisiloxane (sold under the name “Silatrizole” by Rhodia Chimie) or methylene bis-benzotriazolyl tetramethylbutylphenol (sold in the solid form under the trade name “Mixxim BB/100” by Fairmount Chemical or in the micronized form in aqueous dispersion under the trade name “Tinosorb M” by Ciba Specialty Chemicals),

[0067] anthranilic compounds, in particular menthyl anthranilate (sold under the trade name “Neo Heliopan MA” by Haarmann and Reimer),

[0068] imidazoline compounds, in particular ethylhexyl dimethoxybenzylidene dioxoimidazoline propionate,

[0069] benzalmalonate compounds, in particular polyorganosiloxane comprising benzalmalonate functional groups (sold under the trade name “Parsol SLX” by Hoffmann-LaRoche),

[0070] and their mixtures,

[0071] the inorganic photoprotective agents selected from the group consisting of pigments or alternatively nanopigments (mean size of the primary particles: generally between 5 nm and 100 nm, preferably between 10 nm and 50 nm) formed from coated or uncoated metal oxides, such as, for example, titanium oxide (amorphous or crystalline in the rutile and/or anatase form), iron oxide, zinc oxide, zirconium oxide or cerium oxide nanopigments, which are all UV photoprotective agents well known per se; or conventional coating agents, such as alumina and/or aluminium stearate; the nanopigments formed from coated or uncoated metal oxides are disclosed in particular in Patent Applications EP 518 772 and EP 518 773.

[0072] The organic photoprotective agents which are more particularly preferred are selected from the group consisting of ethylhexyl salicylate, ethylhexyl methoxycinnamate, octocrylene, benzophenone-3, 4-methylbenzylidene camphor, 2,4,6-tris(diisobutyl 4′-aminobenzalmalonate)-s-triazine, anisotriazine, ethylhexyl triazone, diethylhexyl butamido triazone, methylene bis-benzotriazolyl tetramethylbutylphenol, drometrizole trisiloxane, and their mixtures.

[0073] The photoprotective agents are generally present in the compositions according to the invention in proportions ranging from 0.1 to 20% by weight with respect to the total weight of the composition and preferably ranging from 0.2 to 15% by weight with respect to the total weight of the composition.

[0074] In another advantageous aspect of the invention, the composition used can additionally comprise at least one other active principle which stimulates dermal macromolecules or which prevents their decomposition and/or one agent which stimulates the proliferation of fibroblasts or keratinocytes and/or the differentiation of keratinocytes.

[0075] Mention may be made, among the active principles which stimulate dermal macromolecules or which prevent their decomposition, of those which act:

[0076] either on the synthesis of collagen, such as extracts of Centella asiatica; asiaticosides and compounds; ascorbic acid or vitamin C and its compounds, synthetic peptides, such as iamine, biopeptide CL or the palmitoyloligopeptide sold by Sederma; peptides extracted from plants, such as the soybean hydrolysate sold by Coletica under the trade name Phytokine®; and plant hormones, such as auxins;

[0077] or on the synthesis of elastin, such as the extract of Saccharomyces cerevisiae sold by LSN under the trade name Cytovitin®; and the extract of the alga Macrocystis pyrifera sold by Secma under the trade name Kelpadelie®;

[0078] or on the synthesis of glycosaminoglycans, such as the product of fermentation of milk by Lactobacillus vulgaris sold by Brooks under the trade name Biomin yogourth®; the extract of the brown alga Padina pavonica sold by Alban Müller under the trade name HSP3®; and the extract of Saccharomyces cerevisiae available in particular from Silab under the trade name Firmalift® or from LSN under the trade name Cytovitin®;

[0079] or on the synthesis of fibronectin, such as the extract of Salina zooplankton sold by Seporga under the trade name GP4G®; the yeast extract available in particular from Alban Müller under the trade name Drieline®; and the palmitoyl pentapeptide sold by Sederma under the trade name Matrixil®;

[0080] or on the inhibition of metalloproteinases (MMP), such as more particularly MMP 1, 2, 3 or 9. Mention may be made of: retinoids and compounds; oligopeptides and lipopeptides, lipoamino acids; the malt extract sold by Coletica under the trade name Collalift®; extracts of blueberry or of rosemary; lycopene; or isoflavones, their compounds or the plant extracts comprising them, in particular extracts of soybean (sold, for example, by Ichimaru Pharcos under the trade name Flavosterone SB®), of red clover, of flax, of kakkon or of sage;

[0081] or on the inhibition of serine proteases, such as leukocyte elastase or cathepsin G. Mention may be made of: the peptide extract of Leguminosae (Pisum sativum) seeds sold by LSN under the trade name Parelastyl®; heparinoids; and pseudodipeptides.

[0082] Mention may in particular be made, among the active principles which stimulate epidermal macromolecules, such as filaggrin and keratins, of the extract of lupin sold by Silab under the trade name Structurine®; the extract of beech Fagus sylvatica buds sold by Gattefossé under the trade name Gatuline®; and the extract of Salina zooplankton sold by Seporga under the trade name GP4G®.

[0083] The agents which stimulate the proliferation of fibroblasts which can be used in the composition according to the invention can, for example, be selected from the group consisting of plant proteins or polypeptides, extracts, in particular of soybean (for example, a soybean extract sold by LSN under the name Eleseryl SH-VEG 8® or sold by Silab under the trade name Raffermine®); and plant hormones, such as gibberellins and cytokinins.

[0084] The agents which stimulate the proliferation of keratinocytes which can be used in the composition according to the invention comprise in particular retinoids, such as retinol and its esters, including retinyl palmitate; phloroglucinol; the extracts of walnut meal sold by Gattefossé; and the extracts of Solanum tuberosum sold by Sederma.

[0085] The agents which stimulate the differentiation of keratinocytes comprise for example inorganic materials, such as calcium; the extract of lupin sold by Silab under the trade name Photopréventine®; sodium β-sitosteryl sulphate, sold by Seporga under the trade name Phytocohésine®; and the extract of maize sold by Solabia under the trade name Phytovityl®.

[0086] The composition according to the invention can be applied to the skin or mucous membranes. It can thus be used in a cosmetic treatment process for the purpose of preventing and/or treating cutaneous signs of intrinsic ageing, comprising the application of the composition according to the invention to the skin or mucous membranes.

[0087] The examples which follow serve to illustrate the invention without, however, exhibiting a limiting nature. The compounds are, depending on the situation, cited according to chemical names or according to CTFA (International Cosmetic Ingredient Dictionary and Handbook) names.

EXAMPLES Example 1 Accelerated Storage Test

[0088] The aim of this test is to study the decomposition of an oxidation-sensitive hydrophilic active principle after storing for two months at 45° C. Various solutions were prepared and their compositions are collated in the following table: TABLE I Compositions Ascorbic (in water) acid Polymer 1 Polymer 2 Solution A 15% — — (Control 1) Solution B 15% 1% — Solution C 15% — 1% Solution D  5% — — (Control 2) Solution E  5% 1% — Solution F  5% — 1%

[0089] All the solutions are brought to pH 6 with 8.9 mol/l KOH.

[0090] The percentages of the polymers are given as active material.

[0091] Polymer 1: Styrene/maleic anhydride (50/50) copolymer in the form of a 30% ammonium salt in water, sold under the reference SMA1000H® by Atofina.

[0092] Polymer 2: Styrene/maleic anhydride (50/50) copolymer in the form of a sodium salt, sold under the reference SMA1000HNa® by Atofina.

[0093] The degree of decomposition measured is given by the ratio:

(C ₀-C ₂ months)/C ₀

[0094] with C₀ concentration of ascorbic acid at t=0 and C₂ months the concentration of ascorbic acid at t=2 months, under the conditions indicated in the above table.

[0095] The concentration of ascorbic acid is determined by the HPLC technique (LaChrom Merck system). The analytical conditions are as follows:

[0096] Column: Lichrosphere100 RP18 (250 mm)

[0097] Eluent: 0.1M phosphate buffer, pH 2.1

[0098] Flow rate: 1 ml/min

[0099] Detection at 257 nm

[0100] Dilution of the sample such that the concentration of ascorbic acid is between 0.05 and 1 mg/ml.

[0101] The results obtained are collated in the following Table II: TABLE II Degree of decomposition after 2 months at 45° C. (in %) under air, amber under nitrogen, glass bottle aluminium flask Solution A 43 19.4 (Control 1) Solution B 16 13.8 Solution C 17.6 9.7 Solution D 45.4 29.6 (Control 2) Solution E 13.4 4.1 Solution F 9 5.1

[0102] It is found, from Table II, that the stability of ascorbic acid, at a concentration of 5 or 15%, is improved in the presence of Polymer 1 and Polymer 2 of the invention, even in the presence of atmospheric oxygen, in comparison with the control. As the polymers mentioned are hydrophilic, it will be sufficient to add them to an aqueous ascorbic acid solution to stabilize the ascorbic acid.

Example 2 Observation of the Effect of the Addition of a Combinationaccording to the Invention on the Synthesis of Tenascin and of Collagen VII:

[0103] The present example describes the effects of the addition of a combination according to the invention, comprising ascorbic acid and a copolymer according to the invention, on reconstructed skin by observation with a microscope of a skin section with immunohistochimical labelling of the proteins of tenascin and collagen VII.

[0104] 1. Preparation of the Reconstructed Skin

[0105] The reconstructed skin used is prepared according to the protocol described in Asselineau et al. (Models in Dermato. Published by Loire and Maibach, 1987, Vol III, 1-7). The modifications to this protocol are:

[0106] the use of normal adult human dermal fibroblasts in a proportion of 10⁶ cells per equivalent dermis;

[0107] the inoculation of the keratinocytes is carried out in a proportion of 50 000 cells per ring with a diameter of 1.5 cm. The keratinocytes used originate from the same donor and are at passage 1 during the inoculation of the dermal equivalents;

[0108] the duration of the immersion phase is 7 days;

[0109] the duration of the emergence phase is 7 days.

[0110] 2. Addition of the Combination According to the Invention:

[0111] The final change in medium of the immersion phase is carried out in the presence of the combination of ascorbic acid and of the styrene/maleic anhydride copolymer in the form of a 40% sodium salt in water. The culture is subsequently mounted on a grid for the emergence phase (7 days) and, during this phase, all changes in medium (every 2 days) are carried out in the presence of the above combination.

[0112] 3.a. Analysis of Collagen VII

[0113] The reconstructed skins are analysed at the end of the emergence phase. A control sample is systematically prepared and analysed in parallel.

[0114] The samples are taken and frozen in liquid nitrogen. The blocks are produced from Tissue Teck. Collagen of type VII is detected by immunohisto-chemistry on frozen sections with a thickness of 5 μm. The conventional indirect immunofluorescence technique is carried out with an anticollagen VII monoclonal antibody (LH7.2, Chemicon International Inc., USA) and a fluorescein-coupled conjugate (FITC-conjugated Rabbit anti mouse immunoglobulins, DAKO, Denmark).

[0115] 3.b. Analysis of Tenascin

[0116] The protocol used is that described in point 3.a. above, except that, in this case, the tenascin is detected with an antitenascin monoclonal antibody (TN2, Chemicon) and a fluorescein-coupled conjugate (FITC-conjugated Rabbit anti mouse immunoglobulins, DAKO, Denmark).

[0117] 4. Observations:

[0118] On observing with a microscope, it is found that the intensity and the thickness of the fluorescence region corresponding to the dermoepidermal junction is much greater in the sample to which the combination of ascorbic acid and styrene/maleic anhydride copolymer in the form of a 40% sodium salt in water has been added. This was observed both for the analysis of collagen VII and for the analysis of tenascin.

[0119] An increase in the fibroblasts in the lattice with a more perpendicular arrangement of the basal keratinocytes at the dermoepidermal junction is also noticed.

Example 3 O/W Anti-ageing Cream

[0120] The following composition is prepared in a way conventional to a person skilled in the art. Phase A Water 18.33 g Glycerol 3 g Phase B Sorbitan tristearate 0.68 g PEG-40 stearate 1.5 g Cetyl alcohol 3 g Glyceryl stearate 2.25 g Myristyl myristate 1.5 g Ethylhexyl palmitate 1.5 g Hydrogenated polyisobutene 2.5 g Shorea robusta seed butter 1.5 g Butyrospermum parkii (shea butter) fruit 0.5 g Cyclopentasiloxane 7.5 g Phenoxyethanol 1 g Phase C Water 43.94 g Ascorbic acid 5 g Potassium hydroxide (50% solution) 3 g Styrene/maleic anhydride copolymer, 30% ammonium salt 3.3 g in water (SMA1000H ®, Atofina)

[0121] A rich and soft cream is obtained which makes it possible to combat signs of ageing and in which ascorbic acid has good stability over time.

Example 4 O/W Anti-ageing Cream

[0122] The following composition is prepared in a way conventional to a person skilled in the art. Phase A Pentaerythrityl tetraethylhexanoate 6 g Ammonium polyacryloyldimethyl taurate 0.6 g Water 14.95 g Methylparaben 0.2 g Glycerol 3 g Phenoxyethanol 0.5 g Phase B PTFE 4 g Cetearyl alcohol (and) ceteareth-30 1.5 g Octocrylene 7 g Butyl methoxydibenzoylmethane 2 g Ethylhexyl salicylate 5 g Glycolipids 0.5 g Propylparaben 0.1 g Petrolatum 1 g Polysorbate 60 1 g Cetyl alcohol 0.5 g Phase C Caprylyl glycol 0.15 g Glyceryl starch 2 g Phase D Water 41 g Ascorbic acid 5 g Potassium hydroxide (50% solution) 3 g Styrene maleic anhydride copolymer, 40% 2.5 g sodium salt in water (SMA1000HNa ®, Atofina)

[0123] A cream is obtained which is soft and fresh on application, which cream makes it possible to combat wrinkles and fine lines and in which the ascorbic acid has good stability.

[0124] All documents, tests, patents, applications, references, articles, publications, etc. mentioned above are incorporated herein by reference. Where a range or limit is expressed all values and subranges therewithin are expressly included as if written out.

[0125] A preferred stabilizing amount of copolymer is any amount that reduces the amount of decomposition of the active principle after storage at 45C. for 2 months (e.g., 0.5, 1, 2, 3%, etc. reduction in decomposition). Preferably the amount of the reduction in decomposition is 5% or greater (e.g., 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, etc. %). The reduction in decomposition is calculated as [(% decomposition without copolymer−% decomposition with copolymer)/% decomposition without copolymer]×100%.

[0126] The above description sets forth the manner and process of making and using the present invention and enables any person skilled in the art to which it pertains to make and use the same, such enablement being provided in addition for the embodiments of the invention included within the claims recited below. 

1. A method for preventing and/or treating cutaneous signs of intrinsic ageing, comprising applying to skin a composition comprising at least one oxidation-sensitive hydrophilic active principle selected from the group consisting of ascorbic acid and its compounds and at least one maleic anhydride copolymer comprising one or more maleic anhydride comonomer units and one or more comonomer units selected from the group consisting of vinyl acetate, vinyl alcohol, vinylpyrrolidone, olefins comprising from 2 to 20 carbon atoms, and styrene, in a physiologically acceptable medium comprising an aqueous phase.
 2. The method according to claim 1, wherein said method is a method of treating cutaneous signs of intrinsic ageing comprising applying said composition to skin in need thereof.
 3. The method according to claim 1, wherein said method is a method of preventing cutaneous signs of intrinsic ageing comprising applying said composition to skin in need thereof.
 4. The method according to claim 1, wherein the hydrophilic active principle is selected from the group consisting of 5,6-di-O-dimethylsilylascorbate, the dl-α-tocopheryl dl-ascorbyl phosphate potassium salt of ascorbic acid, magnesium ascorbyl phosphate, sodium ascorbyl phosphate and ascorbyl glucoside.
 5. The method according to claim 1, wherein the oxidation-sensitive hydrophilic active principle is ascorbic acid.
 6. The method according to claim 1, wherein the maleic anhydride units of the copolymer are in the hydrolysed form and in the form of alkaline salts.
 7. The method according to claim 1, wherein the oxidation-sensitive active principle and the copolymer are both in the aqueous phase.
 8. The method according to claim 1, wherein the copolymer has a molar fraction of maleic anhydride units of between 0.1 and
 1. 9. The method according to claim 8, wherein the copolymer has a molar fraction of maleic anhydride units of between 0.4 and 0.9.
 10. The method according to claim 1, wherein the copolymer is a copolymer of styrene and of maleic anhydride in a 50/50 ratio.
 11. The method according to claim 1, wherein the copolymer is a copolymer of styrene and of maleic anhydride in a 50/50 ratio in the form of an ammonium or sodium salt.
 12. The method according to claim 1, wherein the molar ratio of the maleic anhydride unit equivalent to the oxidation-sensitive hydrophilic active principle varies between 0.005 and
 10. 13. The method according to claim 1, wherein the molar ratio of the maleic anhydride unit equivalent to the oxidation-sensitive hydrophilic active principle varies between 0.01 and
 1. 14. The method according to claim 1, wherein the copolymer is present at a concentration of between 0.1 and 40% by weight of the aqueous phase.
 15. The method according to claim 1, wherein the copolymer is present at a concentration of between 0.1 and 10% by weight of the aqueous phase.
 16. The method according to claim 1, wherein the composition further comprises at least one non-ascorboc acid active principle which stimulates dermal macromolecules or which prevents their decomposition and/or an agent which stimulates the proliferation of fibroblasts or keratinocytes and/or the differentiation of keratinocytes.
 17. A method for preventing and/or treating cutaneous signs of intrinsic ageing, comprising applying to skin or mucous membranes a composition comprising at least one oxidation-sensitive hydrophilic active principle selected from the group consisting of ascorbic acid and its compounds and at least one maleic anhydride copolymer comprising one or more maleic anhydride comonomer units and one or more comonomer units selected from the group consisting of vinyl acetate, vinyl alcohol, vinylpyrrolidone, olefins comprising from 2 to 20 carbon atoms, and styrene, in a physiologically acceptable medium comprising an aqueous phase. 